Abstract
Cigarette smoking is an environmental risk factor associated with a variety of pathologies including cardiovascular disease, inflammation, and cancer development. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory bladder disease with multiple etiological contributors and risk factors associated with its development, including cigarette smoking. Previously, we determined that cigarette smoking was associated with bladder wall accumulation of platelet activating factor (PAF), a potent inflammatory mediator that facilitates transendothelial cell migration of inflammatory cells from the circulation. PAF has been shown to reduce expression of tight junctional proteins which could ultimately lead to increased urothelial cell permeability. In this study, we observed that cigarette smoke extract (CSE) treatment of human urothelial cells increases PAF production and PAF receptor expression and reduces wound healing ability. After exposure to cigarette smoke for 6 months, wild‐type C57BL/6 mice displayed urothelial thinning and destruction which was not detected in iPLA 2 β −/− (enzyme responsible for PAF production) animals. We also detected increased urinary PAF concentration in IC/BPS patients when compared to controls, with an even greater increase in urinary PAF concentration in smokers with IC/BPS. These data indicate that cigarette smoking is associated with urothelial cell damage that may be a result of increased PAF‐PAF receptor interaction. Inhibition of iPLA 2 β activity or blocking of the PAF‐PAF receptor interaction could serve as a potential therapeutic target for managing cigarette smoke‐induced bladder damage.
Highlights
A sedentary lifestyle, overeating, excessive alcohol consumption, and smoking can contribute directly to many diseases, including diabetes, cardiovascular disease, cancer, and inflammatory diseases (Verheij et al 1981a; McHowat et al 1993a; Sharma et al 2009)
We measured iPLA2 activity in human urothelial cells (HUC) and immortalized urothelial cells from control bladders and interstitial cystitis/bladder pain syndrome (IC/BPS) patients (IC/BPS) in the absence of calcium and using (16:0, [3H]18:1) plasmenylcholine (Fig. 1). iPLA2 activity measured in the presence of (R)-bromoenol lactone ((R)BEL, 5 lmol/L) to inhibit iPLA2c resulted in approximately 50% inhibition of iPLA2 activity (Fig. 1, hatched bars) in all cells tested
In addition to increased platelet activating factor (PAF) production, we observed a significant increase in PAF receptor expression in HUC exposed to cigarette smoke extract (CSE) for 48 h (Fig. 2, right panel)
Summary
A sedentary lifestyle, overeating, excessive alcohol consumption, and smoking can contribute directly to many diseases, including diabetes, cardiovascular disease, cancer, and inflammatory diseases (Verheij et al 1981a; McHowat et al 1993a; Sharma et al 2009). Bladder conditions such as lower urinary tract symptoms (LUTS), urinary tract infections (UTI), interstitial cystitis/bladder pain syndrome (IC/BPS), and bladder cancer have been shown to be influenced by lifestyle choices (Park et al 1994). According to the Interstitial Cystitis Association, IC/BPS patients who smoke have noted symptom improvement upon smoking cessation
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